Gene Mutations Screen In CTnI In Hypertrophic Cardiomyopathy And Genotype-Phenotype Correlation Analysis

Hypertrophic cardiomyopathy (HCM) is a disease characterized by unexplained left and/or right ventricular hypertrophy, which is usually asymmetric and the interventricular septum is most commonly affected. Its typical morphological changes include myocyte hypertrophy and disarray. Its clinical manifestations are chest pain, dyspnea, syncope, arrhythmia and heart failure. Sudden cardiac death (SCD) is the prominent characteristics of HCM, and clinical data show that HCM is the important cause of SCD in young people. The molecular genetics studies have indicated that at least 60-70 percent HCM patients are caused by gene mutations, which are transmitted as an autosomal dominant trait called familial hypertrophic cardiomyopathy (FHCM). Fourteen genes have been reported to be related to HCM so far, 11 of them are genes encoding the sorcomere. The mutations of these genes have been proved closely related to the clinical manifestations of FHCM according to the molecular genetics and clinical studies. CTnI is an important component of Tn complex and plays a crucial role in regulating the excitation-contraction couple of myocardium. For the diagnosis of HCM, it is important and necessary to study the genotype-phenotype correlation of CTnI gene. In this study, we described the genetic characteristics and the genotype-phenotype relationship of CTnl gene in HCM patients.100 unrelated HCM patients (including 51 probands of pedigrees and 49 sporadic patients) and 120 healthy age, gender matched controls were collected. The DNA was extracted from peripheral blood leukocytes. The functional regions of gene cTnl (exon 1-8) were amplified using the polymerase chain reaction (PCR). DNA sequencing was used to detect the mutation and to screen the family members. The database including disease history, symptom, physical examination, two-dimensional echocardiography, electrocardiography (ECG), Doppler echocardiography, catheter or nuclear examination results of the HCM patients and controls were established for the genotype-phenotype correlation analysis.Results and Conclusions: a Argl70Gln missense mutation of cTnl gene was identified in one patient. The 120 controls were normal. It was not reported in the previous studies in Caucasian population, that is, it is a novel HCM-causing mutation. No mutation was found in the family members including the parents of the proband. So, Argl70Gln was considered as the de novo mutation. According to the clinical manifestation analysis, this mutation contributed to the malignant phenotypes and the risk of sudden cardiac death.